title: Diuretics, calciuria and secondary hyperparathyroidism in the Chronic Renal Insufficiency Cohort.
abstract: BACKGROUND
  Secondary hyperparathyroidism is a common complication of chronic kidney disease (CKD) that is associated with bone disease, cardiovascular disease and death. Pathophysiological factors that maintain secondary hyperparathyroidism in advanced CKD are well-known, but early mechanisms of the disease that can be targeted for its primary prevention are poorly understood. Diuretics are widely used to control volume status and blood pressure in CKD patients but are also known to have important effects on renal calcium handling, which we hypothesized could alter the risk of secondary hyperparathyroidism.
  
  
  METHODS
  We examined the relationship of diuretic treatment with urinary calcium excretion, parathyroid hormone (PTH) levels and prevalence of secondary hyperparathyroidism (PTH ≥ 65 pg/mL) in a cross-sectional study of 3616 CKD patients in the Chronic Renal Insufficiency Cohort.
  
  
  RESULTS
  Compared with no diuretics, treatment with loop diuretics was independently associated with higher adjusted urinary calcium (55.0 versus 39.6 mg/day; P < 0.001), higher adjusted PTH [67.9, 95% confidence interval (CI) 65.2-70.7 pg/mL, versus 52.8, 95% CI 51.1-54.6 pg/mL, P < 0.001] and greater odds of secondary hyperparathyroidism (odds ratio 2.1; 95% CI 1.7-2.6). Thiazide monotherapy was associated with lower calciuria (25.5 versus 39.6 mg/day; P < 0.001) but only modestly lower PTH levels (50.0, 95% CI 47.8-52.3, versus 520.8, 95% CI 51.1-54.6 pg/mL, P = 0.04) compared with no diuretics. However, coadministration of thiazide and loop diuretics was associated with blunted urinary calcium (30.3 versus 55.0 mg/day; P <0.001) and odds of hyperparathyroidism (odds ratio 1.3 versus 2.1; P for interaction = 0.05) compared with loop diuretics alone.
  
  
  CONCLUSIONS
  Loop diuretic use was associated with greater calciuria, PTH levels and odds of secondary hyperparathyroidism compared to no treatment. These associations were attenuated in patients who were coadministered thiazides. Diuretic choice is a potentially modifiable determinant of secondary hyperparathyroidism in CKD.
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Tamara
authors.initials: T
authors.lastname: Isakova
authors.forename: Cheryl A M
authors.initials: CA
authors.lastname: Anderson
authors.forename: Mary B
authors.initials: MB
authors.lastname: Leonard
authors.forename: Dawei
authors.initials: D
authors.lastname: Xie
authors.forename: Orlando M
authors.initials: OM
authors.lastname: Gutiérrez
authors.forename: Leigh K
authors.initials: LK
authors.lastname: Rosen
authors.forename: Jacquie
authors.initials: J
authors.lastname: Theurer
authors.forename: Keith
authors.initials: K
authors.lastname: Bellovich
authors.forename: Susan P
authors.initials: SP
authors.lastname: Steigerwalt
authors.forename: Ignatius
authors.initials: I
authors.lastname: Tang
authors.forename: Amanda Hyre
authors.initials: AH
authors.lastname: Anderson
authors.forename: Raymond R
authors.initials: RR
authors.lastname: Townsend
authors.forename: Jiang
authors.initials: J
authors.lastname: He
authors.forename: Harold I
authors.initials: HI
authors.lastname: Feldman
authors.forename: Myles
authors.initials: M
authors.lastname: Wolf
mesh_terms: D000328:Adult; D000368:Aged; D002118:Calcium / Q000652:urine*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004232:Diuretics; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000209:etiology*; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D011379:Prognosis; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000150:complications*; D055815:Young Adult
chemical_list: D004232:Diuretics; D010281:Parathyroid Hormone; D002118:Calcium